1. Field of Invention
This invention relates to an atmospheric RF/DC device, specifically to such RF/DC devices which are used for analyzing gas-phase ions at or near atmospheric pressure.
2. Description of Prior Art
Quadrupole Mass Spectrometry (QMS)
The analytical utility of a RF/DC (radio frequency/direct current) mass filter or analyzers, such as a quadrupole mass filter, as a device for continuous selection and separation of ions under conventional vacuum conditions is well established. It also has a highly developed theoretical basis (for example see, Paul et al. (1953), Dawson (1976), Miller et al. (1986), Steel et al. (1999), Titov (1998), Gerlich (1992). The desirable performance attributes of the quadrupole mass filter is the fact that motion in the x, y, and z directions are decoupled, (i.e. motion in each direction is independent of motion of the other directions in the Cartesian coordinate system, see Dawson (Chapter 2, 1976)). In general, a time varying potential is applied to opposite sets of parallel rods as illustrated in FIG. 1.
The “hyperbolic” geometry in the x-y plane coupled with the appropriate time-varying applied potential (an RF field) creates a pseudo-potential well that will trap ions within a “stable” mass range along the centerline of the x-y plane (the z-axis), while ejecting ions of “unstable” mass in the x and y directions. In a quadrupole operated a low pressures (under vacuum, <10−3 torr), motion along the z-axis is generally determined by the initial energy of the ions as they enter the quadrupole field, and can be generally considered equivalent to motion in a field free environment. One notable exception to this field-free model would be the effects the fringing fields at the entrance and exit of the quadruple. At the entrance and exit from quadrupoles the x, y and z motions are coupled. This results in the transfer of small amounts of translational energy between the different dimensions. The effects of which can generally be reduced dramatically through electrode design (e.g. the use of RF-only pre- and post-filters).
Ion motion within a quadrupole is well characterized, and is described by the various solutions of the Mathieu equation (see Dawson (Chapter 3, 1976), Miller et al. (1986), Steel et al. (1998)). Simply stated, for a given ion with a particular mass-to-charge ratio (m/z), there exist sets of RF (alternating at the radio frequency) and DC (direct current) voltages, which when applied to a quadrupole yield stable trajectories. These sets of RF and DC voltages can be plotted to represent regions of stability both in the x and y directions (as shown in FIG. 2A). Since motion in the x and y directions are de-coupled, it is convenient to plot both directions in a single plot, focusing on the region(s) where stable trajectories are possible simultaneously in both the x and y directions. This region of stability is designated the “bandpass region”.
According to the analytical theory based on the Mathieu equation, any set of voltages which do not lie within one of these regions of stability (in both x and y directions) will result in an unstable trajectory of ions, with exponentially increasing acceleration from the centerline of the quadrupole in the unstable direction (x or y). These stability boundaries tend to be very sharp, and can therefore be used to reject certain masses while accepting other masses. Since each mass has a unique set of stable voltages, judicious selection of voltages can allow selection of a narrow bandpass of masses (or one particular mass) to be transmitted through the quadrupole at the expense of all others as illustrated in FIG. 2B. Quadrupole mass spectrometers are typically scanned through the mass range by increasing both RF and DC voltages while maintaining a constant ratio (see “Scan Line” in FIG. 2B). The slope of the scan line determines the resolution of the mass spectrometer.
There is evidence that these stability boundaries observed with convention quadrupole operation are independent of the operating pressure, and therefore achieving a specific mass resolution should be possible even for a quadrupoles operated at higher pressures, such as atmospheric pressure. The majority of research with higher pressures has occurred in the pressure range of 1×10−5 to 1×10−1 torr with the three-dimensional quadrupole ion trap (for example, Johnson et al. (1992), U.S. Pat. No. 4,540,884 to Strafford et al. (1985)) and recently with two-dimensional (2-D) quadrupole linear traps (for example, U.S. Pat. No. 5,420,425 to Bier et al. (1995) and U.S. Pat. No. 6,797,950 to Schwartz et al. (2004); and commercialized by Applied Biosystems/MDS Sciex of Foster City, Calif., USA (see http://www.appliedbiosystems.com) and Thermo Electron Corp. of San Jose, Calif., USA (see http:/www.thermo.com)). It has been clearly observed with three-dimensional quadrupole ion traps that stability boundaries may actually be sharpened at these higher pressures yielding improved resolution. But there are limits with the operating pressures. As the pressure is increased in quadrupole devices the incidence of a gas discharge increases as illustrated in the studies of ion pipes by Bruce Thomson and coworkers (Thompson et al. (1995)).
FIG. 3 illustrates that there are two pressure regimes where time-varying fields can be established at sufficient field strength to affect the radial displacement of unstable ions; the first is at low pressures (<10−2 torr, where existing 2- and 3-D quadrupole mass analyzers and traps are operated) and the second is at or near atmospheric pressure (760 torr, the present invention). The region marked forbidden at intermediate pressures is limited by gas discharge at the higher voltages required for quadrupole mass filtering. In addition, scattering effects from discrete collisions between ions and the surrounding gases deleteriously affect the motion of the ions in the intermediate pressure region as well.
Ion Mobility Spectrometry (IMS)
In recent years ion mobility spectrometry (IMS) has become an important analytical tool for measurement of ionized species created in a wide variety of atmospheric pressure ion sources; including but not limited to, discharge, 63Ni, and photo-ionization (Eiceman et al. (1994), Hill et al. (1990)). Recently, a number of researchers have also incorporated LC/MS sources, such as, electrospray (ES) and atmospheric pressure chemical ionization (APCI) into IMS (Wyttenbach et al. (1996), Wittmer et al. (1994), Covey et al. (1993), Guevremont et al. (1997)).
One recent non-conventional implementation of IMS (known as FAIMS, high-field asymmetric waveform ion mobility spectrometry) utilizes an asymmetric waveform to isolate ions between parallel plates or concentric tubes (Buryakov et al. (1993), U.S. Pat. No. 5,420,424 to Carnahan et al. (1995), Purves et al. (1999), W.O. patents 00/08456 (2000) and 00/08457 (2000) both to Guevremont et al., and commercialized by lonalytics, Corp. (Ottawa, Calif., http://www.ionalytics.com) as an LC/MS interface). This technique demonstrates the principal that we propose with the present invention, in that it utilizes a flow of gas along the z-axis coupled with alternating field conditions to create a bandpass spectrometer. Of particular note is the ability to produce field strengths of well over 10,000 volts per cm without discharge occurring. When coupled to ES and mass spectrometry FAIMS has served as an effective means of fractionation of various molecular weight regimes (Ells et al. (1999)).
Recent work by Miller and coworkers (U.S. Pat. Nos. 6,495,823 (2002), 6,512,224 (2003), 6,690,004 (2004), 6,806,463 (2004), 6,815,668 (2004) 6,815,669 (2004), 6,972,407 (2005); and U.S. patent application publications 2003/0132380 (2003) and 2004/0094704 (2004)) have introduced a miniaturized differential mobility device, microDMx™ (see SIONEX, Corp., Bedford, Mass., USA, http://www.sionex.com) and are now selling the device complete with electronics and as a component for incorporation into analytical devices, for example, gas chromatography-differential mobility detectors: CP-4900 by Varian, Inc. (Palo Alto, Calif., USA, http://www.varianinc.com) and EGIS Defender™ by Thermo, Inc. (Waltham, Mass., USA, http://www.thermo.com).
In a separate implementation of ion mobility, an ion mobility storage trap, both 2- and 3-dimensional traps, with asymmetric alternating current (AC) and variable direct current (DC) potentials has been proposed—for example, in the U.S. Pat. No. 6,124,592 to Sprangler (2000). Although these ion trapping devices may be able to trap ions, but once the ions are trapped ejecting the ions from the trap is very difficult due to lack of inertia of the ions at higher pressures, especially at, near, and above atmospheric pressure. These devices must rely on ions drifting very slowly out of the trap.
Our patent U.S. Pat. No. 6,784,424 B1 (2004) disclosed many of the same components of the present invention; however, the present invention distinguishes itself from our own prior art by disclosing improved ion sample introduction, alternative operating modes, and improved ion detection alternatives that yield better specificity and selectivity.
Nevertheless all the RF/DC mass filters or analyzers, linear and three-dimensional quadrupoles, IMS, FAIMS, and DMS heretofore known suffer from a number of disadvantages:
(a) Conventional quadrupole mass filters require the need for components, such as vacuum chambers, high-vacuum electrical feed-throughs, etc., that can withstand large pressure differences (−1,000 torr). This necessitates the need for stainless steel, aluminum, or other materials; chambers with vacuum tight welds; or metal or rubber seals that can withstand the large pressure difference.
(b) Conventional quadrupole mass filters require the need for expensive high vacuum pumps, such as turbomolecular or diffusion pumps; and low vacuum pumps, such as mechanical vane pumps; both costing several thousands of dollars. The cost of these pumps can makeup approximately 20% of the total cost of an instrument.
(c) Atmospheric interfaces for quadrupole mass filters require expensive high vacuum pumps for operation, resulting in costly and complex interface designs.
(d) Quadrupole mass filters weight several hundred pounds and require a substantial amount of electrical power for operation, heating and cooling, etc.; all restricting their portability.
(e) These all add to the manufacturing cost of quadrupole mass spectrometers and filters thereby resulting in a large percentage (−50%) of the cost of mass analyzers being due to the cost of the vacuum system components, including the vacuum pumps (both high and low vacuum), chamber, vacuum feed-throughs; atmospheric pressure interfaces; etc.
(f) FAIMS and other IMS analyzers lack the precision and band pass capabilities of quadrupolar designs or other multi-pole designs, by utilizing only 2 parallel plates instead of multiple poles. For example, in FAIMS and other asymmetrical RF devices, by utilizing asymmetric RF voltages between parallel plates these devices are forming only one-half of the fields seen in quadrupolar designs, therefore stopping short of the precision and band-pass capabilities of quadrupolar devices.
(g) 2- and 3-dimensional ion trapping devices while having the ability to trap ions with symmetric (and asymmetric) RF and DC potentials, lack sufficient axial forces to move ions from inside the device to the outside where they may be detected or samples through apertures or capillaries.
(h) All of these designs suffer from a very inefficient sampling of atmospheric gas-phase ions into the area between the parallel plates.